Melatonin Potentiates the Curative Effect of Mesenchymal Stem Cells in Subcortical White Matter Tissues of Cuprizone Treated Mice Model of Multiple Sclerosis

Aim of the Work: : The aim of the present study is to examine if melatonin may potentiate the positive effect of Bone Marrow Mesenchymal stem cells BM-MSCs for Induced Multiple Sclerosis (MS) model in subcortical white matter tissues
Materials and Methods: 30 mice were categorized into 5 groups. Group (1), control group. The animals of groups (2, 3, 4 and 5) were nourished with food comprising 0.3% cuprizone for 4 weeks for induction of the demyelination in subcortical white matter. Group (2) was directly euthanized after 4 weeks of cuprizone feeding. Group (3) the animals were intravenously injected via tail 1x10⁶ BM –MSCs and euthanized after 4 weeks. Group (4) the animals were given intraperitoneal daily doses (5 mg/kg) of melatonin and euthanized after 4 weeks. Group (5) the animals were given BM-MSCs, as in Group (3), and melatonin, as in Group (4), and then euthanized after 4 weeks.
Results: The histo-pathological examination of subcortical white matter tissues revealed that cuprizone induced sever alterations in fascicles with notable increase in glial fibrillary acidic protein (GFAP) immunoexpression (IE), loss in sliver impregnation satin, and ultrathin examination showed various morphological changes in myelin sheath. After treatment of animals with BM-MSCs definite improvement could be detected in white matter tissues. Moreover, melatonin administration ameliorates the negative effect of cuprizone. All the findings nearly regressed after coadministration of BM-MSCs + melatonin.
Conclusion: BM-MSc and/or melatonin have a potential remylination effect in MS mouse model.